Pilomatrix carcinoma is a rare adnexal tumor with origin from the germinative matrical cells of the hair follicle. Clinically, it presents as a solitary lesion commonly found in the head and neck region as well as the upper back. The tumors cannot be distinguished by their clinical appearance only and frequently are mistaken for cysts. Histopathologic examination provides the definitive diagnosis in most cases. These carcinomas are aggressive neoplasms with a high probability of local recurrence and distant metastasis. Assessment of the Wnt signaling pathway components such as β-catenin, lymphoid enhancer-binding factor 1 (LEF-1), and caudal-related homeobox transcription factor 2 (CDX-2) potentially can be used for diagnostic purposes and targeted therapy.
We report a rare and unique case of early pilomatrix carcinoma with intralesional melanocytes. We review the molecular pathology and pathogenesis of these carcinomas as well as the significance of early diagnosis.
Case Report
A 73-year-old man with a history of extensive sun exposure presented with a 1-cm, raised, rapidly growing, slightly irregular, purple lesion on the right forearm of 3 months’ duration with tendency to bleed. He did not have a history of skin cancers and was otherwise healthy. Excision was recommended due to the progressive and rapid growth of the lesion.
Histopathologic Findings—Gross examination revealed a 0.9×0.7-cm, raised, slightly irregular lesion located 1 mm away from the closest peripheral margin. Histologically, the lesion was a relatively circumscribed, dermal-based basaloid neoplasm with slightly ill-defined edges involving the superficial and deep dermis (Figure 1A). The neoplasm was formed predominantly of sheets of basaloid cells and small nests of ghost cells, in addition to some squamoid and transitional cells (Figure 1B). The basaloid cells exhibited severe nuclear atypia, pleomorphism, increased nuclear to cytoplasmic ratio (Figure 1C), minimal to moderate amounts of eosinophilic cytoplasm, enlarged nuclei, prominent nucleoli, and coarse chromatin pattern. Abundant mitotic activity and apoptotic bodies were present as well as focal area of central necrosis (Figure 1C). Also, melanophages and a multinucleated giant cell reaction was noted. Elastic trichrome special stain highlighted focal infiltration of the neoplastic cells into the adjacent desmoplastic stroma. Melanin stain was negative for melanin pigment within the neoplasm. Given the presence of severely atypical basaloid cells along with ghost cells indicating matrical differentiation, a diagnosis of pilomatrix carcinoma was rendered.
FIGURE 1. A, Histopathology of a pilomatrix carcinoma revealed a dermal-based neoplasm with irregular borders formed predominantly of basaloid cells (H&E, original magnification ×20) (reference bar, 2 mm). B, The neoplasm was formed of basaloid shadow cells (red stars) and squamoid cells (H&E, original magnification ×200) (reference bar, 200 μm). C, Marked cytologic atypia of basaloid cells with increased mitoses and focal necrosis also were present (H&E, original magnification ×200) (reference bar, 200 μm).
Immunohistochemistry—The neoplastic cells were diffusely positive for p63, CDX-2 (Figure 2A), β-catenin (Figure 2B), and CD10 (Figure 2C), and focally and weakly positive for cytokeratin (CK) 5, BerEP4 (staining the tumor periphery), androgen receptor, and CK18 (a low-molecular-weight keratin). They were negative for monoclonal carcinoembryonic antigen, epithelial membrane antigen, CK7, CK20, CD34, SOX-10, CD56, synaptophysin, and chromogranin. Cytokeratin 14 was positive in the squamoid cells but negative in the basaloid cells. SOX-10 and melanoma cocktail immunostains demonstrated few intralesional dendritic melanocytes.
FIGURE 2. A–C, Immunohistochemistry revealed the tumor cells were positive for caudal-related homeobox transcription factor 2, β-catenin, and CD10 (original magnifications ×40, ×20, and ×20, respectively) (reference bars: 600 μm, 2 mm, and 2 mm, respectively).
Comment
Pilomatrix carcinoma is a rare malignant cutaneous adnexal neoplasm with origin from the germinative matrix of the hair bulb region of hair follicles. Pilomatrix carcinoma was first reported in 1980.1,2 These tumors are characterized by rapid growth and aggressive behavior. Their benign counterpart, pilomatrixoma, is a slow-growing, dermal or subcutaneous tumor that rarely recurs after complete excision.
As with pilomatrixoma, pilomatrix carcinomas are asymptomatic and present as solitary dermal or subcutaneous masses3,4 that most commonly are found in the posterior neck, upper back, and preauricular regions of middle-aged or elderly adults with male predominance.5 They range in size from 0.5 to 20 cm with a mean of 4 cm that is slightly larger than pilomatrixoma. Pilomatrix carcinomas predominantly are firm tumors with or without cystic components, and they exhibit a high probability of recurrence and have risk for distant metastasis.6-15